Comparative in vitro pharmacodynamics of BO-2727, meropenem and imipenem against Gram-positive and Gram-negative bacteria

Abstract

Objective: To investigate and compare the in vitro pharmacodynamics of three carbapenems: imipenem, meropenem and BO-2727.Methods: The following studies were performed: (1) comparative studies of the rate of killing of the three carbapenems of reference strains of Gram-positive and Gram-negative bacteria at a concentration corresponding to the 1-h serum level following 500 mg intravenously in humans; (2) comparative studies of the rate of killing of BO-2727, meropenem and imipenem at different antibiotic concentrations of reference strains of Gram-positive and Gram-negative bacteria; (3) comparative studies of the rate of killing of BO-2727, meropenem and imipenem of bacteria which are phenotypically tolerant; (4) studies of the postantibiotic effect of BO-2727 using viable counts and optical density; (5) studies of the postantibiotic sub-MIC effect (PA SME) of BO-2727 using optical density.Results: No difference in killing rate was noted between the three carbapenems, and there was no concentration-dependent killing of the Gram-negative strains after 6 h. A pronounced paradoxical effect was seen against Staphylococcus aureus. All three antibiotics were able to kill phenotypically tolerant bacteria. Only very short or no postantibiotic effect of BO-2727 was found against the investigated strains. Very long PA SMEs were noted for the Gram-negative strains, although there was a pronounced variation for the different strains of Pseudomonas aeruginosa.Conclusion: There was no significant difference between the studied carbapenems in their pharmacodynamic properties. All three antibiotics acted similarly to other β-lactam antibiotics